Four general lines of fundamental and applied immunologic investigations are focused on the pathologic consequences of immunologic malfunction. First, the precise cellular requirements for the induction and maintenance of immunologic tolerance will be investigated with special emphasis on the possible role of suppressor T cells and the esponsive state of specific B cells in tolerant animals. Second, several aspects of viral interactions with host gene products of the cell membrane will be examined including: the specificity of virus specific T cells particularly regarding the H2-viral antigen complex and the possible role of the MHC as a viral receptor. Third, considerable effort will be devoted to analysis of the mediators of immunologic injury. Studies of the C system will include: molecular characterization of the alternate pathway and particularly its bacteriacidal effect, nature of bond between the membrane attack complex and membrane lipids, role of C in T and K cell killing, participation of C in human disease, chemistry of C1r and its conversion and the role of C, particularly factor B of the properidin system, in activation of macrophages. The Hageman factor system will be examined in an attempt to identify the essential stimulant in kinin formation. Fourth, a number of experimentally induced and spontaneous animal and human immunologic diseases in which immune complexes (1C) are involved will bestudied. Quantitation of 1C formation and localization of deposition will be undertaken in chronic serum sickness in the rabbit. In a variety of experimental situations the scavenging action of the RES and of the glomerular mesangi will be measured and their participation in the initiation of IC glomerular disease determined. The presence of circulating IC resulting from transplantation of normal or malignant tissues will be quantitated and correlated between such IC and course of tissue graft determined. Using the Raji assay to isolate IC from the blood in both immunologic and neoplastic diseases attempts will be made to identify their antigenic components in hopes of revealing etiologic agents. Finally, the murine SLE-like syndrome found in several strains will be further analyzed virologically, genetically and immunologically in order to elucidate the etiologic and essential pathogenetic elements of this disease.